PROJECT SUMMARY/ABSTRACT. Most cases of wrist osteoarthritis (OA) are a form of degenerative arthritis associated with severe pain. Because a functional, pain free wrist is essential for a functional hand, wrist OA precludes many tasks of everyday life (i.e. opening a door, carrying groceries). One of the most common surgical treatments for severe wrist OA, proximal row carpectomy (PRC), involves removal of the entire proximal row of carpal bones, shortening the forearm-to-hand length. This procedure is successful in relieving pain and improving function relative to an untreated wrist. However, compared to a healthy wrist, PRC often yields decreased range of motion and loss of grip strength. The cause of these functional deficits following PRC is not understood. Following PRC, forearm-to-hand length is decreased without concomitant surgical shortening of muscle-tendon units. As a result, surgeons have an anecdotal assumption that post-PRC deficits arise, in part, because the muscle-tendon units are relatively long, or ?slackened? due to the surgery. However, studies in animal models and our preliminary data in humans suggest that, when maintained in a shortened position for an extended time, muscles lose sarcomeres in series, resulting in atrophy and increased passive stiffness. Based on these objective studies, we hypothesize that the limb shortening imposed by PRC results in decreased serial sarcomere number and muscle volume, decreasing active muscle force-generating capacity. We will test our hypothesis by implementing novel, in vivo imaging techniques in both limbs of individuals with unilateral PRCs. We will quantify interlimb differences in serial sarcomere number (Aim 1) and muscle volume (Aim 2) and determine their contributions to functional deficits. We will measure sarcomere length via second harmonic generation microendoscopy, fascicle length using extended field-of-view-ultrasound, and both tendon length and muscle volume using 3D ultrasound. From these data, we will identify chronic differences in muscle structure following PRC limb shortening by calculating serial sarcomere number (optimal fascicle length) and physiological cross-sectional area. Quantitative biomechanical measures of muscle function and clinical impairment, including passive joint torques and maximum isometric grip force, will also be assessed. Quantifying muscle-tendon structural adaptations to this chronic limb shortening will inform the development of more effective rehabilitation protocols and surgical interventions for individuals with severe wrist OA. The proposed research will develop experimental skills necessary to link muscle structural changes to clinical deficits. In addition, training on surgical and rehabilitation treatments, effective teaching and mentoring, collaborating and communicating with scientific and clinical audiences, and clear, succinct scientific writing skills are planned. This training and research will provide the necessary experiences and skills to pursue a career as an independent researcher in an academic setting.